An integrated regulatory network including two positive feedback loops to modulate the activity of sigma(E) in mycobacteria.

sigma(E), one of the best characterized mycobacterial extracytoplasmic function sigma factors, is involved in virulence, surface stress response and modulation of the inflammatory response during infection. The regulation of its activity is very complex and involves transcriptional, translational and post-translational control. Post-translational regulation is controlled by RseA, an anti-sigma factor belonging to the zinc-associated anti-sigma factor family. In this issue of Molecular Microbiology, Barik et al. demonstrate that RseA is a redox-sensing protein that is able to bind sigma(E) only in reducing environment. Importantly, they describe a novel positive feedback loop responsible for sigma(E) release and activation following surface stress, due to ClpC1P2-dependent proteolytic degradation of RseA, depending on its phosphorylation by the eukaryotic-like Ser/Thr protein kinase PknB.